Chronic Fatigue Syndrome and the Brain

Chronic fatigue syndrome affects as many as four in a thousand people in the United States—perhaps more. Despite that, there's been slow progress in understanding the disease, and researchers still aren't exactly sure what causes it. Now, a small new study hints that subtle differences in the brain's white matter might have something to do with the disease.

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CFS has a controversial past. For years, health officials denied it even existed, ironically dismissing it as a sign of mental illness. But in the last few years, more and more researchers are taking it seriously. The latest research points to mold-produced toxins as a likely cause—or at least trigger—of CFS, the symptoms of which include impaired memory and concentration, extreme fatigue after exercise, muscle and joint pain, and unrefreshing sleep. Yet exactly how CFS works remains something of a mystery.

Using standard fMRI, the researchers discovered that CFS patients' brains generally had less white matter—the long, fiber-like nerves that transmit electrical signals between different parts of the brain—than those of control subjects.

One avenue worth exploring is brain imaging, Stanford researcher Michael Zeineh and colleagues write today in the journal Radiology, though previous brain studies of patients with CFS have yielded inconsistent results. To probe deeper, Zeineh and company used standard functional magnetic resonance imaging, or fMRI, along with a technique called diffusion tensor imaging, which helps researchers and doctors examine microscopic properties of brain tissues. Using those methods, the team compared the brains of 15 patients with CFS, identified using the so-called Fukuda definition, and a control group of 14 healthy people who'd been chosen to match the CFS group on traits such as age and gender.

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Using standard fMRI, the researchers discovered that CFS patients' brains generally had less white matter—the long, fiber-like nerves that transmit electrical signals between different parts of the brain—than those of control subjects. On its own, that's not really that surprising.

What was truly odd was what went on in a white-matter tract called the right arcuate fasciculus, which connects the frontal and temporal lobes of the brain. There, diffusion tensor imaging revealed signs of stronger nerve fibers running along parts of the right arcuate fasciculus, or possibly weaker nerve fibers crossing it—in theory, a sign of a better-connected brain. Odder still, that effect was strongest in patients with the most severe CFS symptoms.

It was "an unexpected finding for a disorder characterized by reduced cognitive abilities," the authors write, though they point out an intriguing recent study suggesting something similar happening in some patients with Alzheimer's disease.

These findings could help doctors better diagnose severe cases of CFS, and they may also help researchers trying to understand the syndrome's origins. Still, the team suggests caution. "Overall, this study has a small number of subjects, so all the findings in this study require replication and exploration in a larger group of subjects," they write.